Chronic Cocaine Use Rewires the Brain

The chronic use of cocaine can lead to structural changes in the brain that make the user more susceptible to addiction.

Researchers at the University of Buffalo and Mount Sinai School of Medicine found that chronic cocaine use reduces the expression of a protein known to regulate brain plasticity in mice, which drives structural changes in the brain, including creating greater sensitivity to the rewarding effects of the drug.

“We found that chronic cocaine exposure in mice led to a decrease in this protein’s signaling,” says David Dietz, Ph.D., assistant professor of pharmacology and toxicology in the School of Medicine and Biomedical Sciences.

“The reduction of the expression of the protein, called Rac1, then set in motion a cascade of events involved in structural plasticity of the brain — the shape and growth of neuronal processes in the brain. Among the most important of these events is the large increase in the number of physical protrusions or spines that grow out from the neurons in the reward center of the brain. This suggests that Rac1 may control how exposure to drugs of abuse, like cocaine, may rewire the brain in a way that makes an individual more susceptible to the addicted state.”

The presence of the spines demonstrates the spike in the reward effect that the user obtains from cocaine, he said. By changing the level of expression of Rac1, Dietz and his colleagues were able to control whether the mice became addicted, by preventing enhancement of the brain’s reward center after exposure to cocaine.

To do the experiment, Dietz and his colleagues used a new tool that allowed for light activation to control Rac1 expression. The researchers say this is the first time that a light-activated protein has been used to modulate brain plasticity.

“We can now understand how proteins function in a very temporal pattern, so we could look at how regulating genes at a specific time point could affect behavior, such as drug addiction, or a disease state,” said Dietz.

Dietz is continuing his research on the relationship between behavior and brain plasticity, looking at how plasticity might determine how much of a drug an animal takes and how persistent the animal is in trying to get the drug.

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